Erwinia Asparaginase After Allergy to PEG-Asparaginase in Treating Young Patients With Acute Lymphoblastic Leukemia

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00537030
First received: September 27, 2007
Last updated: July 2, 2013
Last verified: July 2013
  Purpose

This clinical trial is studying the side effects of Erwinia asparaginase and what happens to the drug in the body in treating young patients with acute lymphoblastic leukemia who are allergic to PEG-asparaginase. Drugs used in chemotherapy, such as Erwinia asparaginase, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.


Condition Intervention
Adult Acute Lymphoblastic Leukemia
Childhood Acute Lymphoblastic Leukemia
Other: laboratory biomarker analysis
Other: pharmacological study
Drug: asparaginase

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacology and Toxicity of Erwinia Asparaginase (Erwinase®; Crisantaspase; IND 290) Following Allergy to PEG-Asparaginase in Treatment of Children With Acute Lymphoblastic Leukemia (ALL)

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Trough serum asparaginase activity [ Time Frame: At 48 hours ] [ Designated as safety issue: No ]
    A Simon "minimax" two-stage design will be used to distinguish between a true response probability of 70% versus a true response probability of 50% with a significance level of 5%, 90% power.


Secondary Outcome Measures:
  • Plasma asparagine depletion [ Time Frame: On days 12 or 13 ] [ Designated as safety issue: No ]
  • Presence of anti-Erwinia asparaginase antibodies in children treated with a course(s) of Erwinase® following clinical allergy to PEG-asparaginase by enzyme-linked immunosorbent assay (ELISA) [ Time Frame: At baseline, prior to doses 4, 5, and 6 and on days 15 and 22 ] [ Designated as safety issue: No ]
    The rate of antibody formation will be described and compared informally to experience in Children's Cancer Group (CCG)-1962 and 1961. Serum asparaginase activity will be compared during Erwinase® courses as an indication of the neutralizing effect of antibodies on the enzyme effect.

  • Frequency of asparaginase-related toxicities following Erwinase® treatment as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: At each course of Erwinase® treatment ] [ Designated as safety issue: Yes ]
    The incidence of these toxicities will be described. The percentage of patients that have Erwinase® therapy discontinued due to the above toxicities will also be estimated. With a sample size of 50, the incidence of the above toxicities can be estimated with a maximum standard error of 7%.


Enrollment: 59
Study Start Date: February 2008
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy)
Patients receive 6 doses of Erwinia asparaginase IM on a Monday/Wednesday/Friday schedule as a replacement for each scheduled dose of PEG-asparaginase remaining on the original treatment protocol. All other chemotherapy continues according to the original treatment protocol.
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Drug: asparaginase
Given IM
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine if the 48-hour trough serum asparaginase activity is ≥ 0.1 IU/mL in young patients with acute lymphoblastic leukemia treated with Erwinia asparaginase after allergy to PEG-asparaginase.

II. To determine the frequency of asparaginase-related toxicity in these patients.

III. To characterize the pharmacokinetics of Erwinia asparaginase in these patients.

SECONDARY OBJECTIVES:

I. To compare serum asparaginase activity and serum asparagine concentration between patients treated with Erwinia asparaginase on this trial and historical controls treated with PEG-asparaginase on CCG-1961 and CCG-1962.

II. To determine the 72-hour serum asparaginase activity on days 8 or 11 or 13 based on the starting date of Erwinia asparaginase therapy.

III. To determine the presence of anti-Erwinia asparaginase antibodies in patients treated with a course(s) of Erwinia asparaginase following clinical allergy to PEG-asparaginase (PEG, pegaspargase).

IV. To determine if serum asparagine is adequately depleted on days 12 or 13 in a subset of these patients.

OUTLINE: This is a multicenter study.

Patients receive 6 doses of Erwinia asparaginase intramuscularly (IM) on a Monday/Wednesday/Friday schedule as a replacement for each scheduled dose of PEG-asparaginase remaining on the original treatment protocol. All other chemotherapy continues according to the original treatment protocol.

Blood samples are collected periodically for pharmacokinetic, pharmacodynamic, and antibody studies.

After completion of study treatment, patients are followed periodically.

  Eligibility

Ages Eligible for Study:   1 Year to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of acute lymphoblastic leukemia
  • Concurrently enrolled on a frontline Children's Oncology Group treatment trial (i.e., COG-AALL0232 or COG-AALL0531, COG-AALL0331, or COG-AALL0434) at a participating institution

    • Must have 1 or more courses of asparaginase remaining to be administered on the treatment protocol
  • Must have had a grade ≥ 2 hypersensitivity reaction to PEG-asparaginase
  • No history of pancreatitis ≥ grade 2
  • No prior Erwinia asparaginase
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00537030

  Show 22 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Wanda Salzer Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00537030     History of Changes
Other Study ID Numbers: AALL07P2, NCI-2009-00316, COG-AALL07P2, CDR0000566349, U10CA098543
Study First Received: September 27, 2007
Last Updated: July 2, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pegaspargase
Asparaginase
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014